Mutational spectrum of bleomycin in lacZ mouse kidney: A possible model for mutational spectrum of reactive oxygen species

Joseph B. Guttenplan, Michael Khmelnitsky, Roderick Haesevoets, Wieslawa Kosinska

Research output: Contribution to journalArticlepeer-review

Abstract

The mutational spectrum of bleomycin was compared with the spontaneous mutational spectrum in lacZ mouse kidney. Mice were treated with four 20 mg/kg of doses of bleomycin over a two-week period, leading to a mutant fraction several times greater than that of controls. The major class of bleomycin-induced mutations consisted of small deletions, in particular -1 deletions at AT base pairs and hot spots for deletions at 5′-GTC-3′ sequences. Smaller, but significant fractions of GC > AT followed by GC > TA substitutions were also observed. In untreated mice, the major class of mutations consisted of GC > AT substitutions followed by GC > TA mutations, and a much smaller fraction of deletions. Other than the specificity of bleomycin for AT base pairs and the 5′-GTC-3′ hotspots, the mutational spectrum of bleomycin in mice is similar to that reported for ionizing radiation. However, bleomycin initially mediates the formation of oxidized DNA via reduction of molecular oxygen, as opposed to the radiolysis of water. In this respect mutagenesis induced by bleomycin may be more similar to that induced by endogenous reactive oxygen species (ROS) than mutagenesis induced by ionizing radiation. If bleomycin-induced mutagenesis is an appropriate model for mutagenesis induced by ROS, then, based on the difference between the mutational spectrum of bleomycin and spontaneous mutagenesis, the latter appears not to result predominantly from ROS, at least in mouse kidney.

Original languageEnglish (US)
Pages (from-to)185-192
Number of pages8
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume554
Issue number1-2
DOIs
StatePublished - Oct 4 2004

Keywords

  • 8-OHdG
  • 8-hydroxydeoxyguanosine
  • Bleomycin
  • CHO
  • Chinese hamster ovary
  • Fe-NTA
  • MF
  • Mutagenesis
  • Mutational spectrum
  • Oxidative damage
  • ROS
  • ferric-nitrilotriacetate
  • mutant fraction
  • reactive oxygen species

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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